Trial Outcomes & Findings for Exercise Intolerance in Renal Failure (NCT NCT01356966)

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

74 participants

Primary outcome timeframe

Baseline, 12 weeks

Results posted on

2015-06-01

Participant Flow

Subjects were recruited from the Atlanta Veterans Affairs (VA) Medical Center from August 2010 to May 2014.

42 subjects were withdrawn prior to group assignment. 16 were screen failures, 7 subjects withdrew, and 19 subjects were terminated early.

Participant milestones

Participant milestones
Measure	Tetrahydrobiopterin + Folate Male subjects with hypertension and chronic kidney disease stage 2 or 3 received Tetrahydrobiopterin (BH4) 200 mg twice daily and folic acid 1 mg daily	Placebo + Folate Male subjects with hypertension and chronic kidney disease stage 2 or 3 received 2 placebo pills twice daily and folic acid 1 mg daily
Overall Study STARTED	18	14
Overall Study COMPLETED	16	12
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Tetrahydrobiopterin + Folate Male subjects with hypertension and chronic kidney disease stage 2 or 3 received Tetrahydrobiopterin (BH4) 200 mg twice daily and folic acid 1 mg daily	Placebo + Folate Male subjects with hypertension and chronic kidney disease stage 2 or 3 received 2 placebo pills twice daily and folic acid 1 mg daily
Overall Study Withdrawal by Subject	1	2
Overall Study Physician Decision	1	0

Baseline Characteristics

Exercise Intolerance in Renal Failure

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tetrahydrobiopterin + Folate n=18 Participants Male subjects with hypertension and chronic kidney disease stage 2 or 3 received Tetrahydrobiopterin (BH4) 200 mg twice daily and folic acid 1 mg daily	Placebo + Folate n=14 Participants Male subjects with hypertension and chronic kidney disease stage 2 or 3 received 2 placebo pills twice daily and folic acid 1 mg daily	Total n=32 Participants Total of all reporting groups
Age, Continuous	57.5 years STANDARD_DEVIATION 1.3 • n=5 Participants	55.2 years STANDARD_DEVIATION 2.2 • n=7 Participants	56.4 years STANDARD_DEVIATION 1.8 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	14 Participants n=7 Participants	32 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 12 weeks

Population: Two subjects withdrawn from each arm due to adverse events. Additionally, two subjects from the treatment group and one subject from the placebo group were not included in this analysis because an adequate MSNA neurogram was unable to be obtained at the end of the study.

Outcome measures

Outcome measures
Measure	Tetrahydrobiopterin + Folate n=14 Participants Male subjects with hypertension and chronic kidney disease stage 2 or 3 received Tetrahydrobiopterin (BH4) 200 mg twice daily and folic acid 1 mg daily	Placebo + Folate n=11 Participants Male subjects with hypertension and chronic kidney disease stage 2 or 3 received 2 placebo pills twice daily and folic acid 1 mg daily
Change in Resting Muscle Sympathetic Nerve Activity (MSNA)	-7.5 bursts/minute Standard Error 2.1	3.2 bursts/minute Standard Error 1.3

SECONDARY outcome

Timeframe: Baseline, 12 weeks

The augmentation index (AIx) is a measure of systemic arterial stiffness, and is defined as the ratio of augmentation (Δ P) to central pulse pressure and expressed as percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. The mean AIx for each group was estimated as an average and expressed as a change from baseline to 12 weeks.

Outcome measures

Outcome measures
Measure	Tetrahydrobiopterin + Folate n=18 Participants Male subjects with hypertension and chronic kidney disease stage 2 or 3 received Tetrahydrobiopterin (BH4) 200 mg twice daily and folic acid 1 mg daily	Placebo + Folate n=14 Participants Male subjects with hypertension and chronic kidney disease stage 2 or 3 received 2 placebo pills twice daily and folic acid 1 mg daily
Change in Mean Central Augmentation Index (AIx)	-5.8 percent Standard Error 2.0	1.8 percent Standard Error 1.7

SECONDARY outcome

Timeframe: Baseline, 12 weeks

The augmentation index (AIx) is a measure of systemic arterial stiffness, and is defined as the ratio of augmented aortic pressure (Δ P) to central pulse pressure expressed as a percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. Because heart rate (HR) affects AIx, AIx was corrected to a HR of 75 beats per minute (bpm) as follows: HR-corrected AIx = -0.39 x (75 - HR) + AIx. The mean AIx for each group was estimated as an average and expressed as a change from baseline to 12 weeks.

Outcome measures

Outcome measures
Measure	Tetrahydrobiopterin + Folate n=18 Participants Male subjects with hypertension and chronic kidney disease stage 2 or 3 received Tetrahydrobiopterin (BH4) 200 mg twice daily and folic acid 1 mg daily	Placebo + Folate n=14 Participants Male subjects with hypertension and chronic kidney disease stage 2 or 3 received 2 placebo pills twice daily and folic acid 1 mg daily
Change in Heart-rate-corrected Augmentation Index (AIx)	-3.2 percent Standard Error 2.1	1.1 percent Standard Error 1.2

Adverse Events

Tetrahydrobiopterin + Folate

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Placebo + Folate

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Tetrahydrobiopterin + Folate n=18 participants at risk Male subjects with hypertension and chronic kidney disease stage 2 or 3 received Tetrahydrobiopterin (BH4) 200 mg twice daily and folic acid 1 mg daily	Placebo + Folate n=14 participants at risk Male subjects with hypertension and chronic kidney disease stage 2 or 3 received 2 placebo pills twice daily and folic acid 1 mg daily
Gastrointestinal disorders Nausea	5.6% 1/18 • Number of events 1	0.00% 0/14
General disorders Dysgeusia	0.00% 0/18	7.1% 1/14 • Number of events 1
Renal and urinary disorders Acute Kidney Injury	5.6% 1/18 • Number of events 1	0.00% 0/14
Injury, poisoning and procedural complications Eye injury	0.00% 0/18	7.1% 1/14 • Number of events 1

Additional Information

Dr. Jeanie Park

Emory University

Phone: 404-727-1386

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place